Corneal endothelial cell plays the most important role in the maintenance of corneal transparency. However, it is said to hardly grow or regenerate in the body. When the corneal endothelial cell is damaged, therefore, the damaged part cannot be filled with a grown cell, and the wound healing tries to fill the clearance by enlarging the cell surface area by cell expansion/migration and compensatory expansion. As a result, the density per unit area of the corneal endothelial cell decreases. Accordingly, when a wound is healed by increasing the surface area of the corneal endothelial cell, the corneal function is naturally limited, and when it collapses, diseases such as bullous keratopathy and the like are developed.
The only method for treating such visual disorders caused by the decrease in the number of corneal endothelial cells is corneal transplantation alone. However, as the situation stands, patients are forced to stand by for a long time due to the extreme shortage of cornea donors all over the world except US. In addition, the cure rate of transparency by transplantation in the eye with a decreased number of corneal endothelial cells is not high, and problems occur in that the corrected visual acuity after surgery is not sufficient and the like. Thus, the treatment by corneal transplantation is not entirely the best treatment method.
As a method for developing a treatment method replacing the conventional corneal transplantation, patent document 1 proposes a corneal reconstruction method applying regenerative medicine and including culturing and transplanting an isolated and cultured corneal endothelial cell. The non-patent document 1 also discloses a culture method characterized by a combination of many kinds of growth factors and extracellular matrices (ECM). Moreover, non-patent document 2 discloses a culture method using a bovine brain hypophysis extract, and non-patent document 3 discloses a culture method including culture on ECM produced, by bovine corneal endothelial cell. However, the proliferation efficiency of corneal endothelial cell by these methods is still unsatisfactory.
When a cultured cell is used for therapeutic purposes, reduction of the risk of infection with a transplantation material needs to be considered. Since the culture methods of non-patent document 2 and non-patent document 3 use bovine brain hypophysis and eyeball, which are designated to be the high risk sites of Bovine Spongiform Encephalopathy (BSE) infection, they have a high risk of infection of BSE.
As a method of transplanting a corneal endothelial cell sheet produced as cornea for transplantation to the corneal stroma back side, a method including removing the entire cornea, adhering a corneal endothelial cell sheet and putting the cornea back in place (non-patent document 4), a method including sclerocorneal incision, wrapping a cultured corneal endothelial cell sheet with a silicon sheet, and delivering the sheet into the anterior chamber with forceps from the incised region, and the like have been employed (non-patent document 5). However, these transplantation methods have problems in that they require high technique of the operator, accompany severe invasion, and damage corneal endothelial cells during the transplantation.